January 5, 2013

Endocannabinoid System Plays A Decisive Role In Motivation For Exercise

A research team from Inserm has published a new study in the journal Biological Psychology detailing the key role played by a protein, the CB1 cannabinoid receptor, during physical exercise. The team demonstrated, in studies conducted on mice, the location of this receptor - in a part of the brain associated with motivation and reward systems - controls the amount of time for which an individual will carry out voluntary physical exercise.

A prior study, performed by scientists at Inserm in 2008, highlighted the many preventive health benefits of regular physical activity. In today's industrial society, however, our activity is limited. This is partly explained by social causes, but these limits are rooted in biology as well.

The inability to experience pleasure during physical activity, which is often quoted as one explanation why people partially or completely drop out of physical exercise programs, is a clear sign that the biology of the nervous system is involved," explains Francis Chaouloff, research director at Inserm´s NeuroCentre Magendie.

The underlying neurobiological mechanisms for physical inactivity have yet to be identified. Chaouloff and his team have begun the task of deciphering these mechanisms. They have already identified the endogenous cannabinoid — endocannabinoid — system as playing a decisive role, particularly one of the brain receptors in this system. The relationship between the endocannabinoid system — target of delta9-tetrahydrocannabinol (the active ingredient of cannabis) — and physical exercise has been implied before. Scientists discovered a decade ago physical exercise activates the endocannabinoid system in trained athletes. It's exact role, however, remained a mystery for years.

Three years ago, the research team observed that when given the chance to use a running wheel, mice lacking the CB1 cannabinoid receptor ran for shorter times and distances than mice with this receptor. CB1 is the principal receptor for the endocannabinoid system in the brain.

The new study focuses on understanding how, where and why the lack of CB1 receptor reduces voluntary exercise performance (by 20 to 30%) in mice allowed access to a running wheel three hours per day.

The use of several strains of mutant — missing the CB1 receptor — mice, along with pharmacological tools, allowed the team to make several discoveries. First, they demonstrated the CB1 receptor controlling running performance is located at the GABAergic nerve endings. Next, they discovered the receptor is located in the ventral tegmental area of the brain, which is an area involved in motivational processes relating to reward. This area is the same whether the reward is natural (food, sex) or associated with the consumption of psychoactive substances.

Based on prior studies and these results, the team suggests the following explanation: at the beginning and for the duration of physical exercise, the CB1 receptor is constantly stimulated by the endocannabinoids, lipid molecules that naturally activate this receptor in response to pleasant stimuli (rewards) and unpleasant stimuli (stress). This stimulation during physical exercise inhibits the release of GABA, an inhibitory neurotransmitter that controls the activity of the dopamine neurons associated with the motivation and reward processes. The authors claim the stimulation "inhibits inhibition," by activating the dopaminergic neurons in the ventral tegmental area. To carry on exercising longer, the CB1 receptor must be stimulated, and the body must receive the necessary motivation.

The “GABAergic brake” continues to act on the dopaminergic neurons in the ventral tegmental area without CB1 stimulation, leading to the reduced performance levels observed in the mice.

Scientists already knew CB1 receptors play a regulatory role in the motivation to consume rewards, natural or not. The unique aspect of this study is that it shows physical exercise can be added to the array of natural rewards regulated by the endocannabinoid system.

“If confirmed, this motivational hypothesis would imply that the role played by the CB1 receptor has more to do with ℠staying power´ in the exercise than with actual physical performance levels,” explain the researchers.

The findings of this study open up new avenues of research into the physiological mediators of pleasure — and even addiction — associated with physical exercise.

“After endorphins, we now need to consider endocannabinoids as another potential mediator of the positive effects that physical exercise has on our mood,” the researchers conclude.